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The Role of ERK1/2 Activation in Sarpogrelate-Mediated Neuroprotection

Cristy A Ku1, Renee C Ryals1, Dan Jiang1

  • 1Casey Eye Institute, Oregon Health & Science University, Portland, Oregon, United States.

Investigative Ophthalmology & Visual Science
|January 26, 2018
PubMed
Abstract

Insights

Sarpogrelate protects the retina by transiently activating the MAPK/ERK pathway, which helps prevent light-induced oxidative stress and apoptosis. This pathway contributes to, but doesn't fully explain, the neuroprotective effects.

Area of Science:

  • Ophthalmology
  • Neuroscience
  • Pharmacology

Background:

  • Retinal neuroprotection is crucial for maintaining vision.
  • The 5-HT2A serotonin receptor plays a role in retinal health.
  • Light exposure can induce retinal damage and cell death.

Purpose of the Study:

  • To identify the signaling molecules mediating 5-HT2A receptor-driven retinal neuroprotection.
  • To investigate the role of the MAPK/ERK pathway in sarpogrelate-induced neuroprotection.

Main Methods:

  • Albino mice received sarpogrelate (a 5-HT2A antagonist) before light exposure.
  • Phosphorylation microarrays and Western blots assessed GPCR signaling and MAPK/ERK activation.
  • MEK inhibitor (MEKi) PD0325901 was used to block ERK1/2.
  • Spectral-domain optical coherence tomography (SD-OCT) and electroretinography (ERG) evaluated neuroprotection.
  • qPCR arrays analyzed gene expression related to oxidative stress and apoptosis.

Main Results:

  • Sarpogrelate treatment activated the MAPK/ERK pathway in a transient manner post-light exposure.
  • Inhibiting ERK1/2 with MEKi attenuated the neuroprotective effects of sarpogrelate.
  • Light exposure altered gene expression in iron metabolism, oxidative stress, and apoptosis.
  • Sarpogrelate prevented these light-induced gene expression changes.

Conclusions:

  • Sarpogrelate-mediated retinal protection involves transient MAPK/ERK pathway activation.
  • The MAPK/ERK pathway is a key mediator but not the sole mechanism of sarpogrelate's neuroprotective action.
  • Sarpogrelate mitigates light-induced retinal damage by modulating oxidative stress and apoptotic gene expression.

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